Deposition of 0.5 to 2 Micron Aerosol in the Human Lung

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DESCRIPTION (provided by the applicant): The deposition of small (less than 2.5Mm) particles in the human lung is governed primarily by the mechanisms of sedimentation and diffusion. Recent studies we performed in the microgravity (MG) environment have shown a significant degree of enhanced deposition of small particles, compared to that predicted by existing numerical models of deposition. It seems likely that this results from the previously unaccounted for effects of the non-reversibility of flows in the human lung (effectively providing enhanced diffusion). Such enhanced deposition means that existing models for small particles (less than 2.5 Mm) probably underestimate exposure, and that this increased exposure occurs in the sensitive alveolar regions of the lung. We propose to investigate enhanced alveolar deposition by studying 1) The contribution of diffusion to aerosol dispersion by inclusion of breathhold in aerosol bolus tests: 2) The increase in convective mixing in the lung caused by flow reversals that induces complex mixing of the streamlines in the lung; and 3) The increase in convective mixing in the lung in 1G by performing similar studies using the smallest particles on the ground. To study these effects, we propose to measure regional deposition and dispersion of inhaled boluses of 0.5 and 2 micron particles in MG in the NASA KC-135 Microgravity research Aircraft, and 0.5 micron particles on the ground. By performing these studies in the absence of gravity we will be able to directly study these effects without the confounding influence of sedimentation, a gravitational process. Such direct observations without the influence of sedimentation are not possible in the terrestrial laboratory. There is evidence for many lung diseases beginning in the small airways or alveoli, and increased alveolar deposition through enhanced diffusion may provide a link between long-term MG exposure and lung disease. The results of this study will allow existing models of regional intrapulmonary aerosol deposition to be improved, especially for the smaller particles (those in the range 0.5 to 1 micron). Such information will provide a much-improved basis for the assessment of exposure to small inhaled particles both in long duration spaceflight and on Earth.